General

**REMS Drug**

Pronunciation:
tek-list-uh-mab

Trade Name(s)

• Tecvayli

Ther. Class.

antineoplastics

Pharm. Class.

T-cell engagers

Indications

Relapsed or refractory multiple myeloma in patients who have previously received ≥4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

Action

Acts as a T-cell engager, binding to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen expressed on the surface of multiple myeloma cells, resulting in facilitated lysis of malignant cells.

Therapeutic Effect(s):

Slowed progression of multiple myeloma.

Pharmacokinetics

Absorption: 72% absorbed following subcut administration.

Distribution: Not extensively distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: Unknown.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• OB:   Pregnancy;
• Lactation:  Lactation.

Use Cautiously in:

• Rep:   Women of reproductive potential
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: arrhythmia, edema, hypertension, hypotension

F and E: hypocalcemia, hyponatremia, hypophosphatemia

GI: constipation, ↓ appetite, diarrhea, HEPATOTOXICITY, hypoalbuminemia, nausea, vomiting

GU: acute kidney injury

Hemat: HEMORRHAGE, NEUTROPENIA, anemia, leukopenia, lymphocytopenia, thrombocytopenia

Local: injection site reactions

MS: pain

Neuro: encephalopathy, fatigue, headache, motor dysfunction, neuropathy, Guillain-Barré syndrome, IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS), SEIZURE

Resp: cough, hypoxia

Misc: CYTOKINE RELEASE SYNDROME (CRS), hypogammaglobulinemia, INFECTION, chills, fever, hypersensitivity reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

May suppress activity of CYP450 drug-metabolizing enzymes (especially within 7 days after first dose and during/after onset of cytokine release syndrome), careful monitoring of  CYP450 substrates  is recommended.

Route/Dosage

SUBQ (Adults): Day 1 (step–up dose 1)– 0.06 mg/kg as single dose;  Day 4 (step–up dose 2)– 0.3 mg/kg as single dose;  Day 7 (1st treatment dose)– 1.5 mg/kg as single dose;  Weekly dosing schedule– 1.5 mg/kg administered 1 wk after first treatment dose and then once weekly thereafter.

Availability

Solution for subcutaneous injection: 10 mg/mL, 90 mg/mL

Assessment

• Monitor for signs and symptoms of CRS (fever, hypoxia, chills, hypotension, sinus tachycardia, headache, elevated liver enzymes). Hold therapy and administer supportive therapy for CRS, may include intensive care for severe or life threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Grade 1 CRS:  If temperature ≥100.4°F (38°C),  hold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose of teclistamab. Grade 2 CRS:  If temperature ≥100.4°F (38°C) with hypotension responsive to fluids and not requiring vasopressors, and/or, oxygen requirement of low-flow nasal cannula or blow-by,  hold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose. Hospitalize patients for 48 hrs following the next dose of teclistamab. Grade 3 CRS:  If temperature ≥100.4°F (38°C) with hypotension requiring one vasopressor with or without vasopressin, and/or, oxygen requirement of high-flow nasal cannula, face mask, non-rebreather mask, or Venturi mask,  First occurrence of Grade 3 CRS with duration <48 hrs, hold teclistamab until CRS resolves. Provide supportive therapy, which may include intensive care. Administer pretreatment medications prior to next dose. Hospitalize patients for 48 hrs following the next dose of teclistamab. For recurrent Grade 3 CRS or Grade 3 CRS with duration ≥48 hrs, permanently discontinue teclistamab. Provide supportive therapy, which may include intensive care. Grade 4: If temperature ≥100.4°F (38°C) with hypotension requiring multiple vasopressors (excluding vasopressin), and/or, oxygen requirement of positive pressure (continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), intubation, and mechanical ventilation), permanently discontinue teclistamab. Provide supportive therapy, which may include intensive care.
• At the first sign of neurologic toxicity, including ICANS, hold teclistamab and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS.Neurologic toxicity, excluding ICANS,  Grade 1 , hold teclistamab until neurologic toxicity symptoms resolve or stabilize.  Grade 2 or first occurrence of Grade 3,  hold teclistamab until neurologic toxicity symptoms improve to ≤Grade 1. Provide supportive therapy.  Grade 3 (Recurrent) or Grade 4,  permanently discontinue teclistamab. Provide supportive therapy, which may include intensive care. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Grade 1, depressed level of consciousness: awakens spontaneously,  hold teclistamab until ICANS resolves. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.  Grade 2, depressed level of consciousness: awakens to voice,  hold teclistamab until ICANS resolves. Administer dexamethasone 10 mg IV every 6 hrs. Continue dexamethasone use until resolution to ≤Grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist; consider starting non-sedating, anti-seizure medicines for seizure prophylaxis. Hospitalize patients for 48 hrs following the next dose of teclistamab.  Grade 3, depressed level of consciousness: awakens only to tactile stimulus, or seizures, either: any clinical seizure, focal or generalized, that resolves rapidly, or non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging, Administer dexamethasone 10 mg IV every 6 hrs. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Hospitalize patients for 48 hrs following the next dose of teclistamab.  Recurrent Grade 3 ICANS: discontinue teclistamab permanently. Administer dexamethasone 10 mg IV and repeat dose every 6 hrs. Continue dexamethasone until resolution to ≤ Grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.  Grade 4, depressed level of consciousness: either patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, OR stupor or coma, or seizures, either life-threatening prolonged seizure (>5 min), or repetitive clinical or electrical seizures without return to baseline in between, OR motor findings: deep focal motor weakness (hemiparesis or paraparesis), OR raised intracranial pressure/cerebral edema, with signs/symptoms such as diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing's triad,  Permanently discontinue teclistamab. Administer dexamethasone 10 mg IV and repeat dose every 6 hrs. Continue dexamethasone until resolution to ≤Grade 1, then taper. Alternatively, consider administration of methylprednisolone 1,000 mg per day IV and continue methylprednisolone 1,000 mg per day IV for ≥2 days. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.
• Monitor for signs and symptoms of infection.  For all grades of infection,  hold teclistamab in patients with active infection during the step-up dosing schedule.  For Grade 3 infections,  hold subsequent doses of until infection improves to ≤Grade 1.  For Grade 4 infections, Consider permanent discontinuation of teclistamab. If not permanently discontinued, hold subsequent doses until infection improves to ≤Grade 1.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

• Monitor liver enzymes and bilirubin at baseline and periodically during therapy. May cause elevated AST and ALT. Hold teclistamab or consider permanent discontinuation of therapy.

Implementation

•  REMS: Teclistamab is available only through the Tecvayli Risk Evaluation and Mitigation Strategy (REMS) due to the risk of CRS and neurologic problems.
• Prior to starting therapy, consider initiation of antiviral prophylaxis to prevent herpes zoster reactivation per guidelines.
• Restarting teclistamab after dose delay:  Step up dose 1: If >7 days since last dose, restart teclistamab step-up dosing schedule at step-up dose 1 (0.06 mg/kg).  Step up dose 2:  If 8 to 28 days since last dose, repeat step-up dose 2 (0.3 mg/kg) and continue teclistamab step-up dosing schedule. If >28 days since last dose, restart teclistamab step-up dosing schedule at step-up dose 1 (0.06 mg/kg).  For any treatment dose:  If 8–28 days since last dose, continue teclistamab weekly dosing schedule at treatment dose (1.5 mg/kg). If >28 days since last dose, restart teclistamab step-up dosing schedule at step-up dose 1 (0.06 mg/kg).
• Administer pretreatment medications (corticosteroid (PO or IV dexamethasone 16 mg, histamine-1 (H1) receptor antagonist (PO or IV diphenhydramine 50 mg), antipyretics (PO or IV acetaminophen 650 mg to 1,000 mg) prior to each dose of the teclistamab step-up dosing schedule.

Patient/Family Teaching

• Explain the purpose of teclistamab to patient.
• Advise patient to notify health care professional promptly if signs and symptoms of CRS (fever (≥100.4°F), feeling anxious, difficulty breathing, confusion or restlessness, chills, headache, dizziness or lightheadedness, increased liver enzymes, fast heartbeat), neurologic problems (headache, confusion, changes in your handwriting, jerking movements, trouble speaking, problems walking, rigid muscles, muscle spasms, muscle weakness in your body or face, feeling restless, tremor, hearing loss, numbness, double vision, burning, throbbing, or stabbing pain tingling), liver problems (tiredness, pain in your right upper abdomen, loss of appetite, dark urine, yellowing of skin or white part of eyes), or upper respiratory infections occur.
• May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to teclistamab is known.
• Rep:   May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for 5 mo after last dose of therapy. Assess immunoglobulin levels in newborns of mothers treated with teclistamab.
• Instruct patient to carry the  Tecvayli  Patient Wallet Card with you at all times and show it to all of your health care professionals. The wallet card lists signs and symptoms of CRS and neurologic problems.

Evaluation/Desired Outcomes

Slowed progression of multiple myeloma.